Adverse drug reaction
An adverse drug reaction (abbreviated ADR) is an expression that describes the unwanted, negative consequences associated with the use of given medications. An ADR is a particular type of adverse effect. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial. The study of ADRs is the concern of the field known as pharmacovigilance. For psychologist two particular classes of reaction are relevent: *Adverse psychiatric reaction to drugs *Adverse psychological reaction to drugs Classification ADRs may be classified by e.g. cause and severity. Cause *Type A: Augmented pharmacologic effects *Type B: Bizarre effects (or idiosyncratic) *Type C: Chronic effects *Type D: Delayed effects *Type E: End-of-treatment effects *Type F: Failure of therapy Types A and B were proposed in the 1970s,Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977:10. and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.Aronson JK. Drug therapy. In: Haslett C, Chilvers ER, Boon NA, Colledge NR, Hunter JAA, eds. Davidson's principles and practice of medicine 19th ed. Edinburgh: Elsevier Science, 2002:147-63. ISBN 0-44307-035-0. Severity The American Food and Drug Administration defines severe effects as: : * Death * Life-Threatening * Hospitalization (initial or prolonged) * Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life. * Congenital Anomaly * - or - * Requires Intervention to Prevent Permanent Impairment or Damage Overall Drug Risk While no official scale exists yet to communicate overall drug risk, the iGuard Drug Risk Rating System is a five color rating scale similar to the Homeland Security Advisory System : * Red (High Risk) * Orange (Elevated Risk) * Yellow (Guarded Risk) * Blue (General Risk) * Green (Low Risk) Location Adverse effects may be local, i.e. limited to a certain location, or systemic, where a medication has caused adverse effects throughout the systemic circulation. For instance, some ocular antihypertensives cause systemic effects Page 146 , although they are administered locally as eye drops, since a fraction escapes to the systemic circulation. Mechanisms As research better explains the biochemistry of drug use, less ADRs are Type B and more are Type A. Common mechanisms are: * Abnormal pharmacokinetics due to ** genetic factors ** comorbid disease states * Synergistic effects between either ** a drug and a disease ** two drugs Abnormal pharmacokinetics Comorbid disease states Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states. Genetic factors Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation. Pharmacogenomics is the study of the inherited basis for abnormal drug reactions. Phase I reactions Inheriting abnormal alleles of cytochrome P450can alter drug metabolism. Tables are available to check for drug interactions due to P450 interactions. . Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolism of drugs such as succinylcholine Phase II reactions Inheriting abnormal N-acetyltransferase which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as isoniazid, hydralazine, and procainamide. Inheriting abnormal thiopurine S-methyltransferase may affect the metabolism of the thiopurine drugs mercaptopurine and azathioprine. Interactions with other drugs The risk of drug interactions are increased with polypharmacy. Protein binding These interactions are usually transient and mild until a new steady state is achieved. OVID full text summary table at OVID These are mainly for drugs without much first-pass liver metabolism. The prinicple plasma proteins for drug binding are: # albumin # α1-acid glycoprotein # lipoproteins Some drug interactions with warfarin are due to changes in protein binding. Cytochrome P450 Patients have abnormal metabolism by cytochrome P450 due to either inheriting abnormal alleles or due to drug interactions. Tables are available to check for drug interactions due to P450 interactions. . Synergistic effects An example of synergism is two drugs that both prolong the QT interval. Assessing causality A simple scale is available at http://annals.org/cgi/content/full/140/10/795. :Note that an ADR should not be labeled as 'certain' unless the ADR abates with dechallenge and recurs with rechallenge are true. A more complicated scale is the Naranjo algorithm. Monitoring bodies Many countries have official bodies that monitor drug safety and reactions. On an international level, the WHO runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies. See also * Adverse effect (medicine) parent concept * Contraindication * Drug interaction * Evidence-based medicine * EudraVigilance (European Union) * FDA * Iatrogenesis * Medical prescription * Paradoxical reaction * Polypharmacy * Responsible drug use * Toxicology * The Medical Letter on Drugs and Therapeutics * Yellow Card Scheme (UK) References External link *Searchable ADR Database Category:Adverse drug reaction Category:Pharmacology